A5023213723- CAR-T cell therapy research
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Viral Infectious Diseases and Gene Expression in Insects
- Neuroblastoma Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Hematopoietic Stem Cell Transplantation
- Acute Lymphoblastic Leukemia research
- SARS-CoV-2 and COVID-19 Research
- Cancer Research and Treatments
- Single-cell and spatial transcriptomics
- RNA Interference and Gene Delivery
- Integrated Circuits and Semiconductor Failure Analysis
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Pancreatic function and diabetes
- COVID-19 Impact on Reproduction
- Cytomegalovirus and herpesvirus research
- Nanowire Synthesis and Applications
- Aquaculture disease management and microbiota
- CRISPR and Genetic Engineering
- Silicon Carbide Semiconductor Technologies
- Bladder and Urothelial Cancer Treatments
Bambino Gesù Children's Hospital
2016-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2013-2025
Immunotherapy with chimeric antigen receptor (CAR)-expressing T cells that target the disialoganglioside GD2 expressed on tumor may be a therapeutic option for patients high-risk neuroblastoma.In an academic, phase 1-2 clinical trial, we enrolled (1 to 25 years of age) relapsed or refractory, neuroblastoma in order test autologous, third-generation GD2-CAR expressing inducible caspase 9 suicide gene (GD2-CART01).A total 27 children heavily pretreated (12 refractory disease, 14 and 1 complete...
Chimeric antigen receptor (CAR) T-cell therapy has been shown to be dramatically effective in the treatment of B-cell malignancies. However, there are still substantial obstacles overcome, before similar responses can achieved patients with solid tumors. We evaluated both vitro and a preclinical murine model efficacy different 2nd 3rd generation CAR constructs targeting GD2, disial-ganglioside expressed on surface neuroblastoma (NB) tumor cells. In order address potential safety concerns...
Abstract Background Paediatric acute myeloid leukaemia (AML) is characterized by poor outcomes in patients with relapsed/refractory disease, despite the improvements intensive standard therapy. The leukaemic cells of paediatric AML show high expression CD123 antigen, and this finding provides biological basis to target chimeric antigen receptor (CAR). However, CAR.CD123 therapy hampered on-target off-tumour toxicity a long “vein-to-vein” time. Methods We developed an off-the-shelf product...
Abstract Chimeric antigen receptor T (CAR-T) cell therapy may achieve long-lasting remission in patients with B-cell malignancies not responding to conventional therapies. However, potentially severe and hard-to-manage side effects, including cytokine release syndrome (CRS), neurotoxicity macrophage activation syndrome, the lack of pathophysiological experimental models limit applicability development this form therapy. Here we present a comprehensive humanized mouse model, by which show...
Abstract Purpose: Medulloblastoma (MB), the most common childhood malignant brain tumor, has a poor prognosis in about 30% of patients. The current standard care, which includes surgery, radiation, and chemotherapy, is often responsible for cognitive, neurologic, endocrine side effects. We investigated whether chimeric antigen receptor (CAR) T cells directed toward disialoganglioside GD2 can represent potentially more effective treatment with reduced long-term Experimental Design: expression...
Objective The aim of this study is to report the safety and efficacy CD19‐targeting chimeric antigen receptor (CAR) T cells in a child with refractory juvenile dermatomyositis (JDM). Methods We describe 12‐year‐old White boy severe, chronically active JDM multiple immunosuppressive treatment lines, including B cell depletion rituximab. patient received single infusion fresh, autologous, second‐generation anti‐CD19 CAR product (lentiviral vector) manufactured on Prodigy device (1 × 10 6...
Abstract Medulloblastoma is the most frequent malignant childhood brain tumor with a high morbidity. Identification of new therapeutic targets would be instrumental in improving patient outcomes. We evaluated expression tumor-associated antigen PRAME biopsies from 60 patients medulloblastoma. was detectable 82% tissues independent molecular and histopathologic subgroups. High also correlated worse overall survival. next investigated relevance as target for immunotherapy. cells were targeted...
The prognosis of many patients with chemotherapy-refractory or multiply relapsed CD30+ non-Hodgkin Lymphoma (NHL) Hodgkin lymphoma (HL) still remains poor, and novel therapeutic approaches are warranted to address this unmet clinical need. In light consideration, we designed pre-clinically validated a Chimeric Antigen Receptor (CAR) construct characterized by anti-CD30 single-chain variable-fragment cassette, linked CD3ζ the signaling domains two costimulatory molecules, namely either...
Chimeric antigen receptor (CAR) T cells directed against CD19 (CART19) are effective in B-cell malignancies, but little is known about the molecular factors predicting clinical outcome of CART19 therapy. The increasingly recognized relevance epigenetic changes cancer immunology prompted us to determine impact DNA methylation profiles on course.We recruited 114 patients with comprising 77 acute lymphoblastic leukemia and 37 non-Hodgkin lymphoma who were treated cells. Using a comprehensive...
T cells engineered with chimeric antigen receptor (CAR-T cells) are an effective treatment in patients relapsed/refractory B-cell precursor acute lymphoblastic leukemia or non-Hodgkin lymphoma. Despite the reported exciting clinical results, CAR-T cell approach needs efforts to improve safety profile, limiting occurrence of adverse events given this treatment. Besides most common side effects, such as cytokine release syndrome and cell–related encephalopathy syndrome, another potential issue...
TcRαβ/CD19-cell depleted HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) represents a new attractive platform for children affected by acute leukemia in need of an allograft and lacking matched donor, disease recurrence being the main cause treatment failure. The use zoledronic acid to enhance TcRγδ lymphocyte function after haplo-HSCT was tested open-label, feasibility, proof-of-principle study. Forty-six high-risk underwent removal TcRαβ+ CD19+ B lymphocytes. No...
Following the third booster dose of mRNA vaccine, Common Variable Immune Deficiencies (CVID) patients may not produce specific antibodies against virus spike protein. The T-cell abnormalities associated with absence are still a matter investigation. Spike-specific IgG and IgA, peripheral T cell subsets, CD40L cytokine expression, T-cells responses were evaluated in 47 CVID 26 healthy donors after three doses BNT162b2 vaccine. Testing was performed two weeks vaccine dose. Thirty-six percent...
Introduction Assessing the response to vaccinations is one of diagnostic criteria for Common Variable Immune Deficiencies (CVIDs). Vaccination against SARS-CoV-2 offered unique opportunity analyze immune a novel antigen. We identify four CVIDs phenotype clusters by integration parameters after BTN162b2 boosters. Methods performed longitudinal study on 47 patients who received 3rd and 4th vaccine dose BNT162b2 measuring generation immunological memory. analyzed specific neutralizing...
Immunocompromised children are at risk of developing severe COVID-19 infection. We conducted a pilot prospective study to evaluate the impact cancer treatment and stem cell transplantation on immunogenicity two doses BNT162b2 vaccine in pediatric patients.Humoral, B- T-cell responses were assessed before, after first second dose patients aged 5–12 years (n = 35) group healthy donors (HD, n 12). Patients divided three groups: solid tumors (ST, 11), hematological malignancies (HM, 14)...
Personalised medicine in oncology needs standardised immunological assays. Flow cytometry (FCM) methods represent an essential tool for immunomonitoring, and their harmonisation is crucial to obtain comparable data multicentre clinical trials. The objective of this study was design a workflow able address the most effective issues contributing intra- interoperator variabilities project. Italian National Institute Health (Istituto Superiore di Sanità, ISS) managed multiparametric flow...
Chimeric antigen receptor T-cells (CAR T-cells) for the treatment of relapsing/refractory B-cell precursor acute lymphoblastic leukemia have led to exciting clinical results. However, CAR T-cell approaches revealed a potential risk CD19-/CAR+ leukemic relapse due inadvertent transduction cells. Background Methods We evaluated impact high percentage blast contamination in patient-derived starting material (SM) on drug product (DP) manufacturing. In vitro as well vivo models were employed...